Functionalized chelants, or bifunctional coordinators, are known to be capable of being covalently attached to an antibody having specificity for cancer or tumor cell epitopes or antigens. Radionuclide complexes of such antibody/chelant conjugates are useful in diagnostic and/or therapeutic applications as a means of conveying the radionuclide to a cancer or tumor cell. See, for example, Meares et al., Anal. Biochem. 142, 68-78, (1984); M. W. Brechbiel et al., Inorg. Chem. 25(16), 2772-2781 (1986); and Krejcarek et al., Biochem. and Biophys. Res. Comm. 77, 581-585 (1977).
Numerous bifunctional chelating agents based on aminocarboxylic acids have been proposed and prepared. For example the cyclic dianhydride of DTPA [Hnatowich et al. Science 220, 613-615, (1983); U.S. Pat. No. 4,479,930] and mixed carboxycarbonic anhydrides of DTPA [Gansow, U.S. Pat. Nos. 4,454,106 and 4,472,509; Krejcarek et al., Biochem. and Biophys. Res. Comm. 77, 581-585, (1977)] have been reported.
Some chelating agents based on functionalized triamines are known. For example, G. H. Searle et al., Aust. J. Chem. 32, 519-36 (1979) teach for the protection of the terminal nitrogens of linear triamines which allows the central nitrogen atom to be functionalized with a methyl group. These compounds were used for the chelation of cobalt ions. When the terminal nitrogen atoms of linear triamines are functionalized with moieties capable of binding to metal ions using the general method disclosed by R. J. Motekaitis et al. [R. J. Motekaitis et al., Inorg. Chem. 23(3), 275-283 (1984)], then a pentadentate chelant is prepared. Additionally the central nitrogen atom is shown to be substituted with a benzyl group. These compounds were also used for the chelation of cobalt ions. A. W. Addison et al., Inorg. Chimica Acta 147, 61-64 (1988) and F. Refosco et al., J. Chem. Soc. Dalton Trans. 611-615 (1988) teach the preparation of a salicylaldehyde Schiff base ligand with a linear triamine in which the central nitrogen atom is functionalized with a methyl group. These compounds are used for the chelation of iron metal ions, and technetium and rhenium metal ions, respectively. E. Chiotellis et al., Nucl. Med. Biol. 15(2), 215-223 (1988) teach the preparation of linear triamines in which the terminal nitrogen atoms are functionalized with alkylthiol moieties. The central nitrogen atom is functionalized with a propyl or a cyclohexyl moiety. The compounds were used for complexation of .sup.99m Tc.
Bifunctional chelating agents derived from triamines are also known. C. H. Paik et al., J. of Radioanal. Chem. 57(2), 553-564 (1980) teach a method to prepare functionalized terminal nitrogen atoms of linear triamines with moieties capable of binding to metal ions and having the central nitrogen atom substituted with a benzylamine group for conjugation to protein. These compounds were used for the chelation of .sup.111 In. Other linear triamine bifunctional chelating agents in which the central nitrogen atom is functionalized are disclosed by C. John et al. in J. Nucl. Med. 29, 814-815 (1988) in which the central nitrogen atom is functionalized with a benzylcarboxylic acid group. These compounds were used for the chelation of .sup.105 Rh and their conjugation with proteins and antibodies.